7/6/ :49:36 AMAravamudhan: Chiral Recognition by NMR1 Distiguishing features for Chirality crowmether-host1.ppt Such small chiral molecules are complexed with larger host molecules and the NMR spectra of the resulting complex is used for recognizing the chiral form, the R or S. Amino acids are designated by L or D optical isomers (equivalent to R,S designation) that corresponds to the presence of asymmetric carbon / a chiral centre. Most of them experimental studies and not much Computational chemistry is reported on such systems for the calculation of chemical shifts of un complexed host and ligand, for a comparison with the complexes. Thus this presentation is a study reporting a small molecule docking with a larger molecule and the use of calculation of chemical shifts on certain model sys tems. Just as much as experimentalists use NMR spectroscopy as an analytical tool for structure determination, it is being pointed out that trends using Chemical shift calculations can be so much useful in modeling studies even if the calculated shift values do not reproduce the experimental shift values. Chiral Recognition by NMR Spectroscopy- A Theoretical approach. Illustrating modeling strategies with organic molecules with overtones for Modeling of Bio-molecules An Abstract S.Aravamudhan This material may be available as Internet Resource: Display the web subdirectory: Some of the linked files in this.ppt file require the Software ARGUSLAB be installed in your system. Download the MS Windows installer setup.exe file by clicking on the link below: And download the all the contents of this directory into the same and single folder in the resident disc of the P.C. for the hyperlinks in the presentation file to display the appropriate file. Download these presentation files from my internet resource: S.Aravamudhan Department of Chemistry North Eastern Hill University SHILLONG Meghalaya

JPG Image Full publication by Bagatur Yants et al 7/6/ :49:36 AM2Aravamudhan: Chiral Recognition by NMR Cs D3d In the D3d all oxygen are disposed towards the cavity of the molecule In the Cs there are interatomic distances for favorable hydrogen bonding Crown Ether 18Crown6 Ether C12H24O6

Crown Ether-18crown6-D3d-webmo computational result The JPG image The JPG Image 7/6/ :49:36 AM3Aravamudhan: Chiral Recognition by NMR The several perspective views of the D3d structure which seems to be occurring more in the polar media

18crown6-Cs form-computational results The JPG Image 7/6/ :49:36 AM4Aravamudhan: Chiral Recognition by NMR The several perspective views of the Cs structure which seems to be occurring more in the nonpolar media

The JPG ImageCrown Ether-18crown6-D3d-webmo computational result 7/6/ :49:36 AM5Aravamudhan: Chiral Recognition by NMR The two-line spectrum of the 18-crown-6 ether, due to the fluctuations and conformational dynamics in solution gives a single averaged line spectrum as much as the cyclohexane (Chair). The experimental PMR spectrum of 18crown6ether displays a single line spectrum at 3.691ppm, this value is higher than the average value of the two-line theoretical spectrum {~( )/2=2.25ppm}. Such differences can be reconciled by using a better QM method of calcualtion (-and a scaling seems inevitable in any case). Link:- data base experimental spectrum as the cyclohexane (Chair). scaling seems inevitable data base experimental spectrum Cyclohexane- CHAIR conformation with similar two line spectrum, requires 5.9 secs CPU time (a fctor of 9 times less). Crown Ether has 42 atoms and Cyclohexane has 18 atoms in the molecule (atom count includes oxygen hetero atom in Crown ether)

The JPG Image 18crown6-Cs form-computational results 7/6/ :49:36 AM6Aravamudhan: Chiral Recognition by NMR Job Str-PMR-CMR-C12H24O6- Crownether-form2-65.JPG Cyclohexane-boat for comparison The NMR spectrum has relatively more complex pattern: A consequence of reduced symmetry of the Molecule. Computationally this requires more CPU time: a difference of about 5 secs as compared to the D 6 d symmetry

The JPG ImageThe Full publication by Koylu et al 7/6/ :49:36 AM7Aravamudhan: Chiral Recognition by NMR The variety of Derivatives of 18- crown-6 ether which are used in the experimental methods; For complexing with chiral molecules and proceed to obtain NMR of the complex. The 18crown6ether in the PMR spectrum has simply a single line; it is not necessary that the derivatives should also have similar single line. Characteristic variations in certain specific nmr line is often possible to recognize the chirality (of the host) dependent variations (as in next slide #7) Typically referred to as NMR titration: A specific line in the spectrum of the complex displays a variation with the relative guest/host concentration ratio.

The JPG Image The Full publication by Koylu et al 7/6/ :49:36 AM8Aravamudhan: Chiral Recognition by NMR The specific NMR line position variation for the S and R conformers. The actual complex (the Host and gust) can be seen in the next slide #8 What makes these kind of studies tedious and prone with ambiguities is: the experimental search for appropriate Guest and Host molecules which would enable some line in the spectrum to be tagged on to distinguish chiral - dependence Hence the query as to whether theoretical calculations would reduce the uncertainties; the quest for appropriate theoretical method is duly the initiative required; Is it then simply a matter of calculating chemical shifts accurately, or the better G.O. possibilities?

The JPG Image The Full publication by Koylu et al This docked complex does indicate that a Theoretical Calculation would entail the complications of docking studies in the macromolecular regime (the hyperlinks should display the AGL files and the corresponding exported images). Thus such a supra molecule studies could derive benefit by modeling with small molecules for favorable features to know the specifics which can then be integrated into a set of conditions for a tangible study of the large molecule. This indication for the necessity for a modeling was pursued to gain some insight; and, the full comprehension of the actualities (regarding the Chiral Recognition by NMR using theoretical methods) would require several compilations of the type presented now, and in the remaining parts.Theoretical Calculation entail the complications of docking studies modelingThis indication for the necessity for a modeling was pursued to gain some insight Hyperlink-1 Hyperlink-2 Aravamudhan: Chiral Recognition by NMR 9 7/6/ :49:36 AM CPUtime-CalcNMRchemShifts.JPG

The JPG Image Computation on Cyclohexane-chair 7/6/ :49:36 AM10Aravamudhan: Chiral Recognition by NMR CYCLOHEXANE-analogous symmetry and conformational disposition Return to Slide #5 A boat conformation requires more CPU time; a marginal difference of about 0.2 secs 1,3,5 trioxane also gives a 2 line NMR

The JPG Image Computation on Cyclohexane-boat 7/6/ :49:36 AM11Aravamudhan: Chiral Recognition by NMR CYCLOHEXANE-analogous symmetry and conformational disposition Return to Slide #6